NRG1 represses yeast-hypha morphogenesis and hypha-specific gene expression in Candida albicans

A M A Murad, P Leng, M Straffon, J Wishart, S Macaskill, D MacCallum, N Schnell, D Talibi, D Marechal, F Tekaia, C d'Enfert, C Gaillardin, F C Odds, A J P Brown

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Abstract

We have characterized CaNrg1 from Candida albicans, the major fungal pathogen in humans. CaNrg1 contains a zinc finger domain that is conserved in transcriptional regulators from fungi to humans. It is most closely related to ScNrg1, which represses transcription in a Tup1-dependent fashion in Saccharomyces cerevisiae. Inactivation of CaNrg1 in C.albicans causes filamentous and invasive growth, derepresses hypha-specific genes, increases sensitivity to some stresses and attenuates virulence. A tup1 mutant displays similar phenotypes. However, unlike tup1 cells, nrg1 cells can form normal hyphae, generate chlamydospores at normal rates and grow at 42 degreesC. Transcript profiling of 2002 C.albicans genes reveals that CaNrg1 represses a subset of CaTup1-regulated genes, which includes known hypha-specific genes and other virulence factors. Most of these genes contain an Nrg1 response element (NRE) in their promoter. CaNrg1 interacts specifically with an NRE in vitro. Also, deletion of two NREs from the ALS8 promoter releases it from Nrg1-mediated repression. Hence, CaNrg1 is a transcriptional repressor that appears to target CaTup1 to a distinct set of virulence-related functions, including yeast-hypha morphogenesis.

Original languageEnglish
Pages (from-to)4742-4752
Number of pages11
JournalEMBO Journal
Volume20
Issue number17
DOIs
Publication statusPublished - 3 Sep 2001

Keywords

  • Candida albicans
  • NRG1 gene
  • transcript profiling
  • transcriptional repression
  • yeast-hypha morphogenesis
  • early growth-response
  • saccharomyces-cerevisiae
  • transcriptional repressor
  • catabolite repression
  • filamentous growth
  • escherichia-coli
  • finger-proteins
  • MIG1
  • SSN6-TUP1
  • promoter

Cite this

Murad, A. M. A., Leng, P., Straffon, M., Wishart, J., Macaskill, S., MacCallum, D., ... Brown, A. J. P. (2001). NRG1 represses yeast-hypha morphogenesis and hypha-specific gene expression in Candida albicans. EMBO Journal, 20(17), 4742-4752. https://doi.org/10.1093/emboj/20.17.4742.